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Chromosomal microarray had highest detection rate for autism spectrum disorder abnormalities
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Chromosomal microarray analysis should be considered as a first-tier genetic diagnostic test for autism spectrum disorders because of its strong ability to detect chromosomal abnormalities in patients with these conditions, findings from a study suggested.
“Most children with autism spectrum disorders [ASD] do not have dysmorphic features or other medical problems associated with a recognizable genetic syndrome, and genetic testing is crucial to identifying the cause for ASD in this population,” researchers wrote.
The researchers from Massachusetts and China used clinical genetic testing for 461 patients aged 13 months to 15 years from the Autism Consortium and 472 patients aged 15 months to 22 years from Children’s Hospital Boston who had clinical diagnoses of ASD between January 2006 and December 2008. Genetic abnormalities were identified through G-banded karyotype, fragile X testing and chromosomal microarray (CMA).
Karyotype testing found abnormal results in 19 of 852 patients (2.23%; 95% CI, 1.73%-2.73%), and fragile X testing revealed abnormalities in four of 861 patients (0.46%; 95% CI, 0.36%-0.56%), according to the researchers.
They reported that CMA, however, identified genomic deletions or duplications in 154 of 848 patients (18.2%; 95% CI, 14.76%-21.64%). Fifty-nine of 848 patients had “abnormal” or “possibly significant” results, which included variants associated with known genomic disorders, whereas 95 had variants of unknown significance. The detection rate for abnormal or possibly significant results by targeted array was 5.3%, and the rate for whole-genome array was 7.3%, according to the researchers.
Ten of 852 patients had normal results according to CMA but exhibited abnormal karyotype due to balanced rearrangements or unidentified marker chromosome, the researchers noted.
They also said the only recurrent copy-number variants were a 1.8-megabase region of chromosome 15q13.2q13.3 (two deletions, two duplications) and a 600-kilobase region of chromosome 16p11.2 (four deletions, two duplications).
“On the basis of our results, genetic diagnosis will be missed in at least 5% of ASD cases without CMA, and our results suggest that CMA with whole-genome coverage should be adopted as a national standard of care for genetic testing among patients with ASDs,” the researchers wrote.
Shen Y. Pediatrics. 2010;125:e727-e735.